Anti-oxidant, anti-inflammatory and anti-fibrosis effects of ganoderic acid A on carbon tetrachloride induced nephrotoxicity by regulating the Trx/TrxR and JAK/ROCK pathway. (1st August 2021)

• Record Type: Journal Article
• Authors: Ma, Jie-Qiong; Zhang, Yu-Jia; Tian, Zhi-Kai
• Is Part Of: Chemico-biological interactions. Volume 344(2021)
• Publication Date: 2021-08-01
• Subjects: Ganoderic acid A -- Renal inflammation -- Fibrosis -- Oxidative stress -- Trx -- JAK; α-SMA α-smooth muscle actin -- GPx glutathione peroxidase -- IL-6 interleukin-6 -- JAK2 the Janus kinase 2 -- NF-κB nuclear factor-κB -- MDA malondialdehyde -- ROCK Rho-associated protein kinase -- SOD superoxide dismutase -- STAT3 signal transducer and activator of transcription 3 -- TGF-β transforming growth factor β -- TNF-α tumor necrosis factor-alpha -- TrxR thioredoxin reductase; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2021.109529
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Ganoderic acid A (GAA), one of the major triterpenoid components extracted from Ganoderma mushroom has been shown to possess numerous important pharmacological activities. The present study was aimed to investigate the mechanisms of GAA on carbon tetrachloride (CCl4 )-induced kidney inflammation, fibrosis and oxidative stress in mice. The male mice were treated with 25 and 50 mg/mg GAA after stimulated with CCl4 . Our results showed that GAA improved renal damage by decreasing the serum levels of creatinine, urea, uric acid and alleviating kidney fibrosis. GAA ameliorated CCl4 -induced indices of inflammation. GAA suppressed oxidative stress by regulating the glutathione antioxidant system and the thioredoxin antioxidant system. GAA increased the activations of thioredoxin reductase (TrxR), Trx, GSH, SOD, GPx. Furthermore, GAA supplementation inhibited the JAK and STAT3 pathway. GAA inhibited the activations of RhoA, ROCK, NF-κB, TGF-β and Smad3. Thus, this study demonstrated that GAA possesses immune-protective properties through regulating the Trx/TrxR, JAK2/STAT3 and RhoA/ROCK pathways. Highlights: Ganoderic acid A ameliorated CCl4 -induced kidney injury in mice. Ganoderic acid A inhibited oxidative stress, inflammation and fibrosis in kidney. Ganoderic acid A activated the GSH and Trx antioxidant system in kidneys. Ganoderic acid A inhibited the JAK/STAT3 and RhoA/ROCK pathways. Ganoderic acid A inhibited the TGF-β1/Smad3 pathways in kidneys of mice.